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  • Title: Effects of aristolochic acid on phospholipase A2 activity and arachidonate metabolism of human neutrophils.
    Author: Rosenthal MD, Vishwanath BS, Franson RC.
    Journal: Biochim Biophys Acta; 1989 Jan 23; 1001(1):1-8. PubMed ID: 2536283.
    Abstract:
    Aristolochic acid is an alkaloid which has recently been shown to have anti-inflammatory activity against edema in mouse foot pads induced by phospholipases A2 from human synovial fluid. The present study has investigated the effects of aristolochic acid on phospholipase activity and arachidonic acid mobilization in human neutrophils. We find that aristolochic acid is a dose-dependent inhibitor of the calcium-dependent neutral active phospholipase A2 isolated from human neutrophils. As much as 90% of the A23187-stimulated release of previously incorporated [3H]arachidonate from intact neutrophils is inhibited by aristolochic acid; the effect is dose-dependent, with an IC50 of 40 microM, and quite rapid, with near maximal inhibition within 5 min. Aristolochic acid inhibits the A23187-stimulated loss of [3H]arachidonate from both choline- and inositol-phospholipids. Decreased release of free [3H]arachidonate is accompanied by a concomitant decrease in synthesis of [3H]leukotriene B4 and [3H]hydroxyeicosatetraenoic acids. Furthermore, aristolochic acid also inhibits the A23187-stimulated synthesis of [3H]alkylacetylglycerophosphocholine from cellular [3H]alkylacylglycerophosphocholine. These results indicate that aristolochic acid is an effective inhibitor of the A23187-stimulated phospholipase A2 activity in human neutrophils.
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